Dandan Chen, Shang Gao, Fei Gao, Ai Liu, Jiangxia Li, Jisheng Li, Qiji Liu
PURPOSE: SMEK1, also known as PP4R3α, the regulatory subunit 3α of serine and threonine phosphatase PP4, participates in diversely critical biological processes such as the integration of centromere, deacetylation of histones, asymmetric divisions of neuroblast, and other crucial cellular activities. SMEK1 was formerly reported to play a part in carcinogenesis. This study aims to reveal the role of SMEK1 in lung adenocarcinoma and the underlying molecular mechanism. METHODS: Using immunohistochemical (IHC) staining, the protein level of SMEK1 in lung adenocarcinoma and adjacent non-tumor tissue was detected...
December 3, 2022: Clinical & Translational Oncology
Christopher Felicelli, Jessica Gulliver, Corey Gray, Andrey Khramtsov, Luis Z Blanco, Nitin R Wadhwani
Somatic malignancies arising in mature teratomas are exceedingly rare entities and even more so are those arising in immature teratomas. Here, we present a unique case of a 13-year-old who initially underwent ovarian sparing cystectomy for a 7.7 cm left ovarian mass with a pre-operative diagnosis of mature cystic teratoma. Histologically, all 3 germ cell layers were present and immature neuroepithelial tubules were also identified. Subsequent sections revealed a nodular lesion composed of neuropil, neuroblasts with a spectrum of maturation, and Schwannian-type stroma...
November 30, 2022: Pediatric and Developmental Pathology
Giuseppe Maria Milano, Daniel Orbach, Michela Casanova, Pablo Berlanga, Reineke A Schoot, Nadege Corradini, Bernadette Brennan, Gema L Ramirez-Villar, Lisa Lyngsie Hjalgrim, Max M van Noesel, Rita Alaggio, Andrea Ferrari
Malignant ectomesenchymoma (MEM) is an extremely rare soft tissue tumor typical of young children, currently included in the category of skeletal muscle malignancies and characterized by a neuroblastic component. This study describes a series of 10 patients prospectively registered in the European paediatric Soft tissue sarcoma Study Group (EpSSG) database Of the 10 cases, seven had an initial local diagnosis of rhabdomyosarcoma. All patients received chemotherapy according to rhabdomyosarcoma strategy, four had radiotherapy...
November 28, 2022: Pediatric Blood & Cancer
Sangeetha Kandoi, Cassandra Martinez, Dana K Merriman, Deepak A Lamba
PURPOSE: The cone-dominant, 13-lined ground squirrel (13-LGS) retina mimics the human central retina, but a thorough examination of retinal development in this species has not been reported. Here, the embryonic and postnatal development of the 13-LGS retina was studied to further characterize 13-LGS as a practical alternative animal model for investigating cone-based vision in health and disease. METHODS: The spatiotemporal expression of key progenitor and cell type markers was examined in retinas from defined embryonic and postnatal stages using immunohistochemistry...
November 1, 2022: Translational Vision Science & Technology
Federica Puglisi, Rachele Soma, Marta Podda, Simona Vetrella, Marco Rabusin, Serena Tropia, Mariaclaudia Meli, Giovanna Russo, Stefania Sorrentino, Giovanni Erminio, Alfredo Pulvirenti, Martino Ruggieri, Andrea Di Cataldo
BACKGROUND: Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest-derived disorders. AIM OF THE STUDY: To explore the occurrence of NBTs within NF1 and to report on its natural history, therapeutic strategies, and outcomes in an Italian cohort of children with NF1 and in the literature...
2022: Frontiers in Pediatrics
V Cantarín-Extremera, M Jiménez-Legido, S Aguilera-Albesa, A Hedrera-Fernández, L Arrabal-Fernández, N Gorría-Redondo, I Martí-Carrera, M E Yoldi-Pedtri, M Sagaseta-De Ilúrdoz, L González-Gutiérrez-Solana
INTRODUCTION: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy. METHODS: We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients...
November 14, 2022: Neurología
Marc Benoit, Mabintou Darboe, Brati Das, Yingying Ge, John Zhou, Annie Yao, Wanxia He, Riqiang Yan, Xiangyou Hu
BACE1 is largely expressed by neurons and is the sole β-secretase for initiating the production of neuronal β-amyloid peptides (Aβ). To fully understand the physiological functions of neuronal BACE1, we used mouse genetic approach coupled with unbiased single nucleus RNA sequencing (snRNAseq) to investigate how targeted deletion of Bace1 in neurons, driven by Thy-1-Cre recombinase, would affect functions in the nervous system. Our transcriptome results revealed that BACE1 is essential for maturation of neural precursor cells and oligodendrocytes in mice...
November 12, 2022: Human Molecular Genetics
Maddalena Sbaffone, Marianna Ruggieri, Michela Sebastiano, Andrew Reay Mackay, Veronica Zelli, Antonietta Rosella Farina, Lucia Annamaria Cappabianca
Neuroblastoma (NB) is a highly malignant embryonic extracranial solid tumor that arises from sympathoadrenal neuroblasts of neural crest origin. In addition to genetic factors, NB has been linked to maternal exposure to a variety of substances during pregnancy. Recent interest in the potential of nutrients to prevent cancer and reduce malignancy has resulted in the identification of several nutraceuticals including resveratrol, curcumin, and molecular components of garlic, which together with certain vitamins may help to prevent NB development...
November 2, 2022: Life
Yunpo Zhao, Jianli Duan, Zhe Han, Ylva Engström, Volker Hartenstein
In Drosophila melanogaster, processing of gustatory information and controlling feeding behavior are executed by neural circuits located in the subesophageal zone (SEZ) of the brain.1 Gustatory receptor neurons (GRNs) project their axons in the primary gustatory center (PGC), which is located in the SEZ.1 , 2 , 3 , 4 To address the function of the PGC, we need detailed information about the different classes of gustatory interneurons that frame the PGC. In this work, we screened large collections of driver lines for SEZ interneuron-specific labeling and subsequently used candidate lines to access the SEZ neuroblast lineages...
November 3, 2022: Current Biology: CB
Kyoko Itoh, Ritsuko Pooh, Osamu Shimokawa, Shinji Fushiki
It is known that somatic activation of PI3K-AKT-MTOR signaling causes malformations of cortical development varying from hemimegalencephaly to focal cortical dysplasia. However, there have been few reports of fetal cases. Here we report two fetal cases of hemimegalencephaly, one associated with mosaic mutations in PIK3CA and another in AKT1. Both brains showed polymicrogyria, multiple subarachnoidal, subcortical, and subventricular heterotopia resulting from abnormal proliferation of neural stem/progenitor cells, cell differentiation, and migration of neuroblasts...
November 3, 2022: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Gustavo Ayala
Nerves not only regulate the homeostasis and energetic metabolism of normal epithelial cells but also are critical for cancer, as cancer recapitulates the biology of neural regulation of epithelial tissues. Cancer cells rarely develop in denervated organs, and denervation affects tumorigenesis, in vivo and in humans. Axonogenesis occurs to supply the new malignant epithelial growth with nerves. Neurogenesis happens later, first in ganglia around organs or the spinal column and subsequently through recruitment of neuroblasts from the central nervous system...
November 2, 2022: Annual Review of Pathology
Sarah Méresse, Vanessa Larrigaldie, Asma Oummadi, Vidian de Concini, Séverine Morisset-Lopez, Flora Reverchon, Arnaud Menuet, Céline Montécot-Dubourg, Stéphane Mortaud
β-N-Methyl-Amino-L-Alanine (BMAA) produced by 95% of cyanobacteria is in constant augmentation with cyanobacteria worldwide proliferation due to global warming and eutrophication. Previously, it has been shown that this contaminant induced neurological disorders, notably by acting as a developmental toxin. However, very few studies focus on the impact of BMAA on neuroglial cells, like astrocytes and microglial cells, in a developmental context. In the present study, we investigated whether BMAA disturbs neurogenesis from mice subventricular zone (SVZ) cells and whether this neurotoxin induces neuroinflammation...
October 26, 2022: Toxicology
Adriana Mañas, Kristina Aaltonen, Natalie Andersson, Karin Hansson, Aleksandra Adamska, Alexandra Seger, Hiroaki Yasui, Hilda van den Bos, Katarzyna Radke, Javanshir Esfandyari, Madhura Satish Bhave, Jenny Karlsson, Diana Spierings, Floris Foijer, David Gisselsson, Daniel Bexell
Chemotherapy resistance and relapses are common in high-risk neuroblastoma (NB). Here, we developed a clinically relevant in vivo treatment protocol mimicking the first-line five-chemotherapy treatment regimen of high-risk NB and applied this protocol to mice with MYCN -amplified NB patient-derived xenografts (PDXs). Genomic and transcriptomic analyses were used to reveal NB chemoresistance mechanisms. Intrinsic resistance was associated with high genetic diversity and an embryonic phenotype. Relapsed NB with acquired resistance showed a decreased adrenergic phenotype and an enhanced immature mesenchymal-like phenotype, resembling multipotent Schwann cell precursors...
October 28, 2022: Science Advances
Nery Jara, Manuel Cifuentes, Fernando Martínez, Iván González-Chavarría, Katterine Salazar, Lucas Ferrada, Francisco Nualart
Although scurvy, the severe form of vitamin C deficiency, has been almost eradicated, the prevalence of subclinical vitamin C deficiency is much higher than previously estimated and its impact on human health might not be fully understood. Vitamin C is an essential molecule, especially in the central nervous system where it performs numerous, varied and critical functions, including modulation of neurogenesis and neuronal differentiation. Although it was originally considered to occur only in the embryonic brain, it is now widely accepted that neurogenesis also takes place in the adult brain...
October 14, 2022: Antioxidants (Basel, Switzerland)
Magnus Zethoven, Luciano Martelotto, Andrew Pattison, Blake Bowen, Shiva Balachander, Aidan Flynn, Fernando J Rossello, Annette Hogg, Julie A Miller, Zdenek Frysak, Sean Grimmond, Lauren Fishbein, Arthur S Tischler, Anthony J Gill, Rodney J Hicks, Patricia L M Dahia, Roderick Clifton-Bligh, Karel Pacak, Richard W Tothill
Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis...
October 21, 2022: Nature Communications
Nkosiphendule Khuthazelani Xhakaza, Pilani Nkomozepi, Ejekemi Felix Mbajiorgu
Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS)...
October 21, 2022: Anatomy & Cell Biology
Lydia M Parkinson, Sarah L Gillen, Laura M Woods, Lewis Chaytor, Daniel Marcos, Fahad R Ali, Jason S Carroll, Anna Philpott
Neuroblastoma is believed to arise from sympathetic neuroblast precursors that fail to engage the neuronal differentiation programme, but instead become locked in a pro-proliferative developmental state. Achaete-scute homolog 1 (ASCL1) is a proneural master regulator of transcription which modulates both proliferation and differentiation of sympathetic neuroblast precursor cells during development, while its expression has been implicated in the maintenance of an oncogenic programme in MYCN-amplified neuroblastoma...
2022: Frontiers in Cell and Developmental Biology
Julia Terreros-Roncal, Miguel Flor-García, Elena P Moreno-Jiménez, Carla B Rodríguez-Moreno, Berenice Márquez-Valadez, Marta Gallardo-Caballero, Alberto Rábano, María Llorens-Martín
The hippocampus hosts the continuous addition of new neurons throughout life-a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single-cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long-standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG)...
October 18, 2022: Hippocampus
Amy L Tan, Saurav Mohanty, Jinbai Guo, Arne C Lekven, Bruce B Riley
In zebrafish, sensory epithelia and neuroblasts of the inner ear form simultaneously in abutting medial and lateral domains, respectively, in the floor of the otic vesicle. Previous studies support regulatory roles for Fgf and Wnt, but how signaling is coordinated is poorly understood. We investigated this problem using pharmacological and transgenic methods to alter Fgf or Wnt signaling from early placodal stages to evaluate later changes in growth and patterning. Blocking Fgf at any stage reduces proliferation of otic tissue and terminates both sensory and neural specification...
October 13, 2022: Developmental Biology
Josephine D Sami, Robert C Spitale, Michael D Cleary
N6 -methyladenosine (m6A) is the most prevalent internal mRNA modification in metazoans and is particularly abundant in the central nervous system. The extent to which m6A is dynamically regulated and whether m6A contributes to cell type-specific mRNA metabolism in the nervous system, however, is largely unknown. To address these knowledge gaps, we mapped m6A and measured mRNA decay in neural progenitors (neuroblasts) and neurons of the Drosophila melanogaster larval brain. We identified 867 m6A targets; 233 of these are novel and preferentially encode regulators of neuroblast proliferation, cell fate-specification and synaptogenesis...
October 15, 2022: Neural Development
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